Biomaterial Database

Blockade of the locomotor stimulant effects of cocaine and methamphetamine by glutamate antagonists. 1993

J M Witkin

Drug Development Group, NIDA Addiction Research Center, Baltimore, MD 21224.

The AMPA antagonist, NBQX, produced dose-dependent blockade of the locomotor stimulant effects of cocaine and methamphetamine in male, Swiss-Webster mice at doses which did not alter spontaneous locomotion. A similar finding was obtained with the competitive NMDA antagonist, NPC 12626, although blockade was only observed at the highest dose studied. The NMDA antagonists, (+)-HA-966 and 7-chlorokynurenic acid (7-CKA), which act at the strychnine-insensitive modulatory site of the NMDA receptor, only blocked the stimulatory effects of methamphetamine and with (+)-HA-966, blockade was only achieved at a dose that decreased spontaneous locomotor activity. These results provide evidence for the involvement of glutamatergic input in the control of behavior involving mesolimbic dopamine. Along with other findings these results suggest that glutamate receptors may be a target for the development of pharmacological therapies for the treatment of psychomotor stimulant abuse and for other disorders involving hyperfunction of the mesolimbic dopamine system (eg. schizophrenia).

UI	MeSH Term	Description	Entries
D007736	Kynurenic Acid	A broad-spectrum excitatory amino acid antagonist used as a research tool.	Kynurenate,Acid, Kynurenic
D008297	Male		Males
D008694	Methamphetamine	A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.	Deoxyephedrine,Desoxyephedrine,Desoxyn,Madrine,Metamfetamine,Methamphetamine Hydrochloride,Methylamphetamine,N-Methylamphetamine,Hydrochloride, Methamphetamine,N Methylamphetamine
D009043	Motor Activity	Body movements of a human or an animal as a behavioral phenomenon.	Activities, Motor,Activity, Motor,Motor Activities
D011760	Pyrrolidinones	A group of compounds that are derivatives of oxo-pyrrolidines. A member of this group is 2-oxo pyrrolidine, which is an intermediate in the manufacture of polyvinylpyrrolidone. (From Merck Index, 11th ed)	Pyrrolidinone,Pyrrolidone,Pyrrolidones
D011810	Quinoxalines		Quinoxaline
D003042	Cocaine	An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.	Cocaine HCl,Cocaine Hydrochloride,HCl, Cocaine,Hydrochloride, Cocaine
D000596	Amino Acids	Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.	Amino Acid,Acid, Amino,Acids, Amino
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus